The objective of this study is to elucidate the basic mechanisms involved in the regulation of erythropoiesis and to apply this knowledge to human erythropoietic diseases. Partially purified preparations of erythropoietin markedly stimulate an increase in the concentration of cyclic GMP in fetal liver erythroid cells. Studies are now being conducted to be certain that it is erythropoietin itself that is producing this effect and to determine the precise cells in which this increase in cyclic GMP is occurring. The polycythemia produced by the Friend virus (FVP) also will be studied. FVP markedly increases erythropoiesis in mice by a mechanism that does not require erythropoietin. The virus will be injected into animals and then the spleen cells will be cultured. Production of lymphocytic leukemia virus and spleen focus forming virus in vitro by the infected cells is being determined. The infected cells will then be separated according to cell type and assayed for the viruses that are present. Since the Friend virus consists of a spleen focus forming virus and lymphocytic leukemia virus each assayed by separate methods, it will be determined whether both of these viruses are present in each of the marrow cells. In addition, an attempt will be made to separate these viruses by several sedimentation techniques. The methods developed in these investigations will be applied to the study of polycythemia vera. Since both the Friend virus erythropoiesis and erythropoiesis in polycythemia vera of human beings proceed without the need for high levels of erythropoietin it is conceivable that both forms of pathologic erythropoiesis occur by a common mechanism.